Dengue viruses (DEN1-4), mosquito-borne members of the family Flaviviridae, are human pathogens of global significance. Of the 1 million annual cases of dengue haemorrhagic fever/dengue shock syndrome, about 2-5% are fatal. Currently, there is no vaccine or antiviral drug to treat DEN infections (Ann, N.Y. Acad. Sci., 951, p. 262-271 (2001), and Clinical Microbiology Reviews, July, p. 480-496 (1998)).
Herbal medicines have emerged as a unique approach for meeting the need for safe, effective and relatively inexpensive new remedies for a variety of disorders. These represent the fastest growing segment among all of alternative medicine. The herbal medicines are produced in different forms, which range from crude, decocted herbs to refined, concentrated and standardized extracts. The health benefit from taking those herbals also varies with the quality of the products and the knowledge of consumers on the products. Some of the products have to be used under a physician's supervision, particularly those indicated for serious diseases although the majority of herbal medicines are generally safe.
Many plants have been scientifically evaluated on experimental models as antiviral agents viz. Acacia nilotica for inhibitory effects on Hepatitis C virus protease (Hussein et. al., Phytotherapy, Res., 14(7) p. 510-16 (2000)), Andrographis paniculata for HIV-1 inhibitory activity (Reddy et. al., Nat. Prod. Res., 19(3): p. 223-30, (2005)), Areca catechu for inhibitory activity on the plaque formation of Herpes simplex virus type-1 (Hattori et. al., Phytotherapy Res., 9, p. 270-276 (1995)), and also for inhibition of Hepatitis B virus DNA polymerase (Chung et. al., Phytotherapy Res, 9, p. 429-434 (1995)), Azadirachta indica for inhibition of replication of Dengue virus type 2 (Parida et. al., J. Ethnopharmacol., 79, p. 273-78 (2002)), Glycyrrhiza glabra for inhibition of growth and cytopathology of several unrelated DNA and RNA viruses and also for inactivating herpes simplex virus irreversibly (Pompei et. al., Nature, 281(5733): p. 689-90 (1979)), Ocimum basilicum for inhibition of DNA viruses viz. herpes virus (HSV); adenovirus (ADV); Hepatitis B and also inhibition of RNA viruses viz. coxsackie virus B1 (CVB1), enterovirus 71 (EV 71) (Chiang et. al., Clin. Exp. Pharm. Physiol., 32, p. 811-16 (2005)), Phyllanthus amarus for suppression of Hepatitis B surface antigen (HBsAg) gene expression in human hepatoma cells (Yeh et. al., Antiviral Res., 20, p. 185-92 (1993)), and for HBsAg clearance (Thyagarajan et. al., Lancet, p. 764-66 (1988)), and Terminalia chebula against herpes simplex virus type 1 infection (Kurokawa et. al., Antiviral Res., 27, p. 19-37 (1995)). Further, antiviral agents of plant origin, being non-toxic and inexpensive, can have easy acceptability (Parida et al, J. Ethnopharmacol., 79, p. 273-278 (2002)).
Though the association of several herbal extracts with antiviral activity is well documented, however, a systematic search for anti-DEN virus activity in plant extracts has not been undertaken so far. It was earlier elucidated that extracts from different parts of plants may yield a source for antiviral compounds (Herrmann et. al., Proc. Soc. Exp. Biol. Med., 124, p. 865-74 (1967)). This prompted several workers to undertake a concerted search for antiviral compounds of plant origin that in turn culminated in a report which showed that a number of plants exhibited efficacy to suppress the growth of several viruses (Aswal et. al., Ind. J. Exp. Biol., 34, p. 444-67 (1996)).
Cissampelos pareira Linn (Family: Menispermaceae, English Name: Velvet Leaf, Hindi Name: Patha, Sanskrit Name: Ambasthaki) is a climbing shrub distributed throughout the warm parts of Asia, East Africa and America and common in India and Ceylon. It is common in warm and dry regions of tropical and sub-tropical parts of India up to an altitude of about 1500 m. It is found in Himachal Pradesh, Chota Nagpur, Bihar, West Bengal, Punjab, Rajasthan particularly in the east of Aravalli, hilly forests of Marathwada, Konkan, Deccan, Bababuden hills of Mysore, Tamil Nadu (Ayurvedic Pharmacopoeia of India, First Edition, Part 1, Vol 1, p. 92-93; Govt of India, Ministry of Health and Family Welfare, Dept of Indian System of Medicine and Homoeopathy, New Delhi; The Wealth of India, A Dictionary of Indian Raw Materials and Industrial Products, Raw Materials, Vol II, Council of Scientific and Industrial Research, Delhi; Database on Medicinal Plants Used In Ayurveda, Vol 2, Central Council for Research in Ayurveda and Siddha, Dept of Indian System of Medicine and Homoeopathy, New Delhi).
Cissampelos pareira Linn is an Ayurvedic medicinal plant used traditionally for the treatment of a number of diseases. It is said to be bitter, astringent, anthelmintic, carminative, stomachic, digestive, anti-inflammatory, diuretic, febrifuge, expectorant, galactogogue and bitter tonic. It is useful in dyspepsia, abdominal pain, diarrhoea, dysentery, fever, cough, coryza, asthma and lactation disorders (Database on Medicinal Plants Used In Ayurveda, Vol 2, Central Council for Research in Ayurveda and Siddha, Dept of Indian System of Medicine and Homoeopathy, New Delhi).
Dengue fever is not mentioned as such in the Ayurvedic classical textbooks; however, many types of “Jwara” have been enumerated in these textbooks along with their signs and symptoms. It is often difficult to correlate one type of “Jwara” as a clinical counter-part of a particular type of “fever” mentioned in the contemporary science. In classical Ayurvedic textbooks, some of the signs and symptoms of Dengue fever do correlate with a type of fever referred to as viz. “Vata-Pittaja Jwara”. The plants which have been mentioned to be used in a condition known as “Vata-Pittaja Jwara”, “Vataj Jwara” and “Pittaj Jwara” in the classical textbooks of Ayurveda were selected and their Ayurvedic attributes were studied which basically falls under the headings viz. “Rasa”; “Guna”; “Veerya”; “Vipaaka”; and “Dosha-Karma”. All these attributes were thoroughly studied for each and every plant and a hypothesis was developed wherein it was postulated that any herb which at least possess viz. Tikta and/or Kashaya Rasa, Laghu and/or Tikshna Guna, Ushna or Sheeta Veerya, having Katu Vipaaka and Vata and/or Pitta Shaamaka would be useful in alleviating signs and symptoms correlating with Dengue fever. Some of the attributes viz. Katu Rasa and Ruksha Guna were in addition to the attributes which were proposed in the hypothesis. Therefore, on the basis of the proposed hypotheses and the presence of proposed, as well as, additional Ayurvedic attributes thereupon, cissampelos pareira Linn (Ambasthaki/Patha) was selected to be undertaken for studying its therapeutic effect in Dengue Fever.